Auhtors: Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, et al.
Abstract
Pirh2 (p53-induced RING-H2 domain protein; also known as Rchy1) is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy, we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes, including a RING domain and a left-handed β-spiral in which three zinc ions align three consecutive small β-sheets in an interleaved fashion. We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53. As a result, Pirh2 preferentially ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53.
Keywords: ubiquitylation, protein
Source: https://www.nature.com/articles/nsmb.1521
Archive: https://archive.is/NTZVo
